Phospho-ULK1 (S556) Recombinant Rabbit Monoclonal Antibody [JE59-28]

Function

ULK1 is an enzyme that in humans is encoded by the ULK1 gene. Unc-51 like autophagy activating kinase (ULK1/2) are two similar isoforms of an enzyme that in humans are encoded by the ULK1/2 genes. It is specifically a kinase that is involved with autophagy, particularly in response to amino acid withdrawal. Not many studies have been done comparing the two isoforms, but some differences have been recorded. Ulk1/2 is an important protein in autophagy for mammalian cells, and is homologous to ATG1 in yeast. It is part of the ULK1-complex, which is needed in early steps of autophagosome biogenesis. The ULK1 complex also consists of the FAK family kinase interacting protein of 200 kDa (FIP200 or RB1CC1) and the HORMA (Hop/Rev7/Mad2) domain-containing proteins ATG13 and ATG101. ULK1, specifically, appears to be the most essential for autophagy and is activated under conditions of nutrient deprivation by several upstream signals which is followed by the initiation of autophagy. However, ULK1 and ULK2 show high functional redundancy; studies have shown that ULK2 can compensate for the loss of ULK1. Nutrient dependent autophagy is only fully inhibited if both ULK1 and ULK2 are knocked out. ULK1 has many downstream phosphorylation targets to aid in this induction of the isolation membrane/ autophagosome. Recently, a mechanism for autophagy has been elucidated. Models have proposed that the active ULK1 directly phosphorylates Beclin-1 at Ser 14 and activates the pro-autophagy class III phosphoinositide 3-kinase (PI(3)K), VPS34 complex, to promote autophagy induction and maturation. Ulk1/2 is negatively regulated by mTORC1 activity, which is active during anabolic-type environmental cues. In contrast, Ulk1/2 is activated by AMPK activity from starvation signals. Ulk1/2 may have critical roles beyond what ATG1 performs in yeast, including neural growth and development.

Background References

1. Deng R et al. MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis. Autophagy. 2021 Oct

2. Cai C et al. Empagliflozin attenuates cardiac microvascular ischemia/reperfusion through activating the AMPKα1/ULK1/FUNDC1/mitophagy pathway. Redox Biol. 2022 Jun

Subcellular Location

Cytoplasm, cytosol, Preautophagosomal structure.

UNIPROT

SwissProt: O75385 Human

SwissProt: O70405 Mouse

Synonyms